Characteristics of Patients With Acute Coronary Syndrome and Lipid Management Status Insights From the Optimal Therapy for All Kagoshima Acute Coronary Syndrome (OK-ACS) Registry

Daisuke Kanda; Akihiro Tokushige; Takashi Kajiya; Takashi Arima; Tetsuro Kataoka; Ryo Arikawa; Mitsuru Ohishi; on behalf of the OK-ACS Registry Group

doi:10.1253/circj.CJ-25-0083

Abstract

Background: With aging of the population, atherosclerotic diseases have increased in Japan, with acute coronary syndrome (ACS) a significant cause of morbidity and mortality. In Kagoshima Prefecture, ACS mortality rates exceed the national average, reflecting challenges in lipid management and access to care.

Methods and Results: The Optimal Therapy for All Kagoshima Acute Coronary Syndrome (OK-ACS) Registry, initiated in April 2022, enrolled 2,328 ACS patients across Kagoshima. This study evaluated the impact of a standardized lipid management pathway, the “Kagoshima Style,” on low-density lipoprotein cholesterol (LDL-C) control and guideline adherence, as well as the regional profile of ACS in Kagoshima. The pathway was implemented at all percutaneous coronary intervention facilities to optimize lipid management and secondary prevention. LDL-C levels decreased significantly (P<0.0001) from admission to discharge and at 3 months (113.3±39.9, 74.6±28.0, and 69.2±25.9 mg/dL, respectively), with no difference according to place of residence. The proportion of patients with LDL-C <70 mg/dL increased from 12% at admission to 59% at 3 months. Maximum tolerated doses of high-intensity statin use increased from 7% at baseline to 9.3% after pathway implementation. Geographic disparities were evident, with patients from isolated islands experiencing delayed treatment access.

Conclusions: The Kagoshima Style pathway improved lipid management, reducing LDL-C and enhancing guideline adherence. This interim analysis provides insights into lipid management and regional disparities in patients with ACS across Kagoshima prefecture.

In Kagoshima Prefecture, the age-adjusted mortality rate (per 100,000 population) for acute myocardial infarction according to the 2020 Vital Statistics was 41.5 for men and 23.3 for women, both higher than the national rate.¹ The high age-adjusted mortality rate for acute myocardial infarction in Kagoshima Prefecture may be related to the unique geographical conditions of many remote islands. However, no detailed survey has yet been conducted to clarify the flow of emergency transport and treatment for patients with acute coronary syndrome (ACS), including acute myocardial infarction.

Ischemic heart disease remains a leading cause of mortality worldwide, with ACS being a critical subset due to its high morbidity and mortality rates. This global health burden is equally significant in Japan, where the aging population exacerbates the prevalence and impact of cardiovascular diseases (CVD). In 2022, heart disease was responsible for 14.8% of all deaths in Japan,² a proportion that underscores the urgent need for effective management strategies to mitigate its healthcare burden.

Hypercholesterolemia is positively correlated with the incidence of coronary artery disease (CAD), with cumulative high cholesterol levels increasing CAD risk.³ Conversely, robust statin therapy, which lowers low-density lipoprotein cholesterol (LDL-C), has effectively reduced cardiovascular events.⁴^,⁵ The ESTABLISH study conducted in Japan demonstrated that early initiation and continuation of statin therapy for patients with ACS significantly reduced plaque volume.⁶ Furthermore, early initiation of statin therapy in patients with ACS is associated with improved long-term clinical outcomes.⁷ Patients with a history of ACS are at high risk of recurrent cardiovascular events,⁸^,⁹ making aggressive lipid-lowering therapy particularly desirable for secondary prevention. Current Japanese guidelines recommend targeting LDL-C levels below 70 mg/dL, advocating for high-intensity statins from the acute phase.¹⁰^,¹¹

Despite these guidelines, adherence rates to high-intensity statin therapy in clinical practice are suboptimal. This variability in adherence to high-intensity statin therapy is observed across different physicians, institutions, and regions, reflecting a broader challenge in consistently applying these guidelines. A recent survey revealed that regional collaborative clinical pathways for patients with ACS have been established in only approximately one-third of Japan’s prefectures, indicating that many regions still lack well-coordinated ACS management.¹² This highlights the importance of structured approaches like the “Kagoshima Style”, a clinical pathway for lipid management after ACS in Kagoshima Prefecture, to improve continuity and standardization of lipid management. In addition, achieving a target LDL-C level of <70 mg/dL remains a significant clinical challenge.¹³ Previous studies in Japan indicate that approximately 50% of patients do not meet this target despite guideline-directed therapy.¹⁴ This gap highlights the need for enhanced strategies and interventions to improve compliance with and treatment outcomes for lipid-lowering therapy in patients with ACS.

Thus, we started an ACS registry, the Optimal Therapy for All Kagoshima Acute Coronary Syndrome (OK-ACS) Registry, with the participation of all hospitals throughout Kagoshima Prefecture that perform percutaneous coronary intervention (PCI) for ACS. In addition, we started an LDL-C management initiative using a clinical pathway for lipid management after ACS (Kagoshima Style) from April 2022. The aims of the OK-ACS Registry are to evaluate the flow of emergency patient transport, including by doctor helicopter, and ACS treatment throughout Kagoshima Prefecture, including remote islands, and to assess the impact of the standardized lipid management pathway on LDL-C control and guideline adherence. This interim analysis provides insights into lipid management and regional disparities in ACS care across Kagoshima Prefecture.

Methods

Study Design

We conducted a retrospective cohort study using medical records extracted from the OK-ACS Registry covering all Kagoshima Prefecture facilities that perform PCI for ACS. The OK-ACS study involves the collaboration of 22 research facilities (Supplementary Table 1). The study will enroll ACS patients treated over 3 years, from April 1, 2022, to March 31, 2025. A 5-year follow-up survey will then be conducted to evaluate treatment outcomes and survey the status at the time of visit and treatment for ACS, including lipid control. The aims of the study are to assess the current treatment landscape, evaluate outcomes, and identify factors influencing treatment efficacy.

Data Collection and Clinical Outcome Measures

Clinical and follow-up data were obtained retrospectively during outpatient visits, by telephone interview, or by obtaining information from the primary physician or clinical research coordinator.

Outcome Measures

We prospectively surveyed the incidence of a composite outcome of major adverse cardiac and cerebrovascular events (MACCE; all-cause mortality, myocardial infarction, and stroke), as well as all-cause mortality, cardiac death, cardiovascular death, myocardial infarction, stroke, and hospitalization due to heart failure.

Other Main Measures

Information regarding place of residence, the facility to which the patient was transported, age, sex, weight, pulse rate, blood pressure, medical history, comorbidities, laboratory data, items related to treatments, time of symptom onset, hospital arrival time, cardiopulmonary arrest within 24 h, cardiogenic shock within 24 h, acute heart failure within 24 h, symptoms within 1 month, walk-in visit, ambulance transport, flight time of a medical helicopter, and whether the patient had been referred from another hospital was obtained.

Lipid profile, hypertension, and diabetes control status were surveyed after 3 months, and every 12 months thereafter.

Inclusion Criteria

Patients aged 20 years or older who received treatment for ACS, including PCI, coronary artery bypass grafting (CABG), or conservative management, within the 3 years leading up to March 31, 2025, were included in the study. No specific exclusion criteria have been established.

The OK-ACS Registry has started implementing a unified lipid management protocol, the “Kagoshima Style,” for patients with ACS at all PCI facilities in Kagoshima Prefecture (Figure 1). In this study, using details for all patients registered up to December 31, 2024, we report on patient information at admission, lipid management interventions centered on statins, and lipid profiles 3 months after discharge.

Figure 1.

Kagoshima Style: secondary prevention clinical pathway for lipid management. ACS, acute coronary syndrome; FH, familial hypercholesterolemia; LDL-C, low-density lipoprotein cholesterol; PCI, percutaneous coronary intervention; PCSK9, proprotein convertase subtilisin/kexin type 9.

Study Participants

Figure 2 shows the study flowchart. In all, 2,328 consecutive patients were enrolled in the OK-ACS Registry from April 1, 2022, to December 31, 2024. Of these patients, 652 with incomplete enrollment or insufficient data and 492 who were censored within 3 months or were not followed up to 3 months were excluded from this analysis. Thus, the final study population for analysis consisted of 1,184 patients (Figure 2).

Figure 2.

Patient flowchart. OK-ACS, Optimal Therapy for All Kagoshima Acute Coronary Syndrome.

Ethical Considerations

This study was reviewed and approved by the Ethics Committee of Kagoshima University Hospital and was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. Obtaining informed consent from patients was not applicable, and an opt-out approach was adopted, whereby public disclosure of the study content to the patients allowed them to request exclusion from the study.

Statistical Analysis

Normally distributed continuous variables are expressed as the mean±SD, whereas those with a skewed distribution are presented as the median with interquartile range (IQR). Categorical variables are presented as frequencies and percentages. Group comparisons for continuous variables were performed using one-way analysis of variance (ANOVA) or the Kruskal–Wallis test, as appropriate. Categorical variables were compared using the Chi-squared test or Fisher’s exact test. Longitudinal changes in continuous variables, such as lipid profiles, were analyzed using multivariate analysis of variance (MANOVA) where applicable. Post hoc comparisons were made using the Bonferroni method to adjust for multiple comparisons. Cochran’s Q test was used for categorical outcomes, such as the proportion of patients achieving LDL-C targets (<70 or <55 mg/dL). Temporal trends were further assessed using Jonckheere–Terpstra tests for continuous variables and Cochran–Armitage trend tests for categorical data. Comparisons of LDL-C levels among the 3 residential groups (i.e., outside Kagoshima City, in Kagoshima City, on an isolated island) were conducted using repeated-measures ANOVA. Two-tailed P<0.05 was considered statistically significant. All statistical analyses were performed using JMP Pro version 17.2 (SAS Institute Inc., Cary, NC, USA) and EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan; http://www.jichi.ac.jp/saitama-sct/SaitamaHP.files/statmedEN.html; Kanda, 2012), a graphical user interface for R version 4.3.1 (R Foundation for Statistical Computing, Vienna, Austria).

This interim analysis focuses on the characteristics of ACS patients and lipid management in Kagoshima Prefecture following the introduction of the Kagoshima Style approach. The clinical outcome measures described in the Methods section are part of the overall OK-ACS study protocol but were not included in this interim analysis. Future research will evaluate long-term outcomes and risk stratification after the completion of the follow-up period.

Results

Patient Characteristics

All Registered Patients The main characteristics of all registered patients are presented in Table 1. Comprehensive details for all registered variables are provided in Supplementary Table 2. The study included 1,184 registered patients with a mean age of 70±13 years, 76.3% of whom were male.

Table 1.

Patient Characteristics for the Entire Cohort and According to Place of Residence

	All (n=1,184)	Place of residence			P value
	All (n=1,184)	Outside Kagoshima City (n=613)	Kagoshima City (n=446)	Isolated island (n=125)	P value
Age (years)	70±13	71±13	69±12	71±12	0.1
Male sex	903 (76.3)	464 (75.7)	348 (78.0)	91 (72.8)	0.43
BMI (kg/m²)	24.2±3.8	24.2±3.9	24.3±3.7	24.4±3.5	0.75
Emergency revascularization	1,093 (92.3)	556 (90.7)	415 (93.0)	122 (97.6)	0.02
Cardiopulmonary arrest within 24 h	34 (2.9)	12 (2.0)	15 (3.4)	7 (5.6)	0.03
Cardiogenic shock within 24 h	83 (7.0)	38 (6.2)	35 (7.9)	10 (8.0)	0.6
Acute heart failure within 24 h	139 (11.7)	82 (13)	42 (9.4)	15 (12)	0.02
Symptoms within 1 month	700 (59.1)	335 (55)	273 (61)	92 (74)	<0.001
Walk-in visit	313 (26.4)	162 (26.4)	113 (25.3)	38 (30.4)	0.53
Ambulance transport	818 (69.1)	430 (70.1)	322 (72.2)	66 (52.8)	<0.001
Doctor helicopter use	44 (3.7)	17 (2.8)	2 (0.4)	25 (20.0)	<0.001
Doctor helicopter flight time (h)	12 [8–30]	8 [6.75–13.25]	19.5 [9–30]	21 [9–38]	0.2
After-hours service	601 (50.8)	297 (48.5)	238 (53.4)	66 (52.8)	0.26
Referrals from other hospitals	585 (49.4)	324 (52.9)	187 (41.9)	74 (59.2)	<0.001
Diagnosis
Acute myocardial infarction	979 (82.7)	480 (78.3)	387 (86.8)	112 (89.6)	<0.001
ST-elevation type	752 (76.8)	369 (76.9)	295 (76.2)	88 (79)
Non-ST-elevation type	227 (23.2)	111 (23)	92 (24)	24 (21)
Unstable angina pectoris	198 (16.7)	131 (21.4)	54 (12.1)	13 (10.4)
Drinking alcohol	443 (37.4)	222 (36.2)	174 (39.0)	47 (37.6)	0.1
Smoker	600 (50.7)	303 (49.4)	233 (52.2)	64 (51.2)	0.12
Hypertension	835 (70.5)	440 (71.8)	298 (66.8)	97 (77.6)	0.049
Use of antihypertensive drugs	727/835 (87.1)	386/440 (87.7)	256/298 (85.9)	85/97 (87.6)	0.14
Diabetes	446 (37.7)	220 (35.9)	173 (38.8)	53 (42.4)	0.43
Use of antidiabetic drugs	358/446 (80)	189/220 (86)	132/173 (76)	37/53 (70)	0.008
Dyslipidemia	633 (53.4)	293 (47.8)	278 (62.3)	62 (49.6)	<0.001
Familial hyperlipidemia	1 (0.72)	1 (1.03)	0 (0)	0 (0)	0.86
Use of lipid-lowering drugs	460 (72.7)	233 (79.5)	189 (68.0)	38 (61.3)	<0.001
Statin	417/460 (90.7)	205/233 (88.0)	177/189 (93.7)	35/38 (92.1)	0.13
Ezetimibe	111/460 (24.1)	50/233 (21.5)	53/189 (28.0)	8/38 (21.1)	0.26
PCSK9 inhibitor	3/460 (0.7)	3/233 (1.3)	0/189 (0)	0/38 (0)	0.23
Others	49/460 (10.7)	30/233 (2.9)	14/189 (7.4)	5/38 (13.2)	0.17
Maximum tolerated doses of high-intensity statin	29/417 (7.0)	11/205 (5.4)	16/177 (9.5)	2/35 (5.7)	0.35
LVEF^A (%)	52.9±12.6	54.0±12.2	51.3±13.3	53.6±11.9	0.003
Previous history
History of bleeding	29 (2.4)	12 (2.0)	15 (3.4)	2 (1.6)	0.09
History of atrial fibrillation	76 (6.4)	37 (6.0)	31 (7.0)	8 (6.4)	0.46
History of myocardial infarction	137 (11.6)	67 (10.9)	56 (12.6)	14 (11.2)	0.55
History of heart failure	82 (6.9)	44 (7.2)	34 (7.6)	4 (3.2)	0.22
History of stroke	127 (10.7)	68 (11.1)	51 (11.4)	8 (6.4)	0.56
History of malignancy	120 (10.1)	71 (11.6)	38 (8.5)	11 (8.8)	0.45
History of active malignancy	29 (24.2)	17 (2.8)	9 (2.0)	3 (2.4)	<0.001
History of poor long-term prognosis	51 (4.3)	47 (7.7)	4 (0.9)	0 (0.0)	<0.001
History of PCI	202 (17.1)	114 (18.6)	71 (15.9)	17 (13.6)	0.29
History of CABG	28 (2.4)	13 (2.1)	13 (2.9)	2 (1.6)	0.48
Complications of PAD	40 (3.4)	14 (2.3)	24 (5.4)	2 (1.6)	0.03
Complications of aortic aneurysm/dissection	17 (1.4)	9 (1.5)	7 (1.6)	1 (0.8)	0.81
Maintenance dialysis	39 (3.3)	22 (3.6)	16 (3.6)	1 (0.8)	0.36
Laboratory data at registration
Creatinine (mg/dL)	0.89 [0.75–1.14]	0.88 [0.73–1.13]	0.9 [0.75–1.18]	0.93 [0.77–1.12]	0.36
eGFR (mL/min/1.73 m²)	60.7±24.0	61.8±25.1	59.5±23.7	59.4±19.0	0.26
HbA1c (NGSP) (%)	6.1 [5.7–6.7]	6.0 [5.7–6.6]	6.1 [5.7–6.8]	6.0 [5.6–7.0]	0.16
Total cholesterol (mg/dL)	187.4±48.5	183.0±46.1	191.1±50.7	190.1±47.6	0.17
HDL-C (mg/dL)	52.5±15.5	53.0±15.8	51.7±14.8	53.3±16.8	0.38
Triglyceride (mg/dL)	114 [76–175]	111 [75–170.5]	119 [77–183.8]	114.5 [75.3–167.3]	0.47
LDL-C (mg/dL)	113±40	105.3±38.9	109.6±43.5	109.7±44.8	0.54

Unless indicated otherwise, data are presented as n (%) for categorical variables and as the median [interquartile range] or mean±SD for continuous variables. Two-tailed P<0.05 was considered significant. ^ALeft ventricular ejection fraction (LVEF) was evaluated by cardiac echocardiography. BMI, body mass index; CABG, coronary artery bypass grafting; eGFR, estimated glomerular filtration rate; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; PAD, peripheral arterial disease; PCI, percutaneous coronary intervention; PCSK9, proprotein convertase subtilisin/kexin type 9.

Distribution by Place of Residence Patient characteristics according to place of residence are presented in Table 1. The patient population exhibited geographic diversity, with 51.8% of patients residing outside Kagoshima City, 37.7% residing within the city, and 10.6% residing on an isolated island (Figure 2). There were no significant differences between the 3 residential groups in mean age and the proportion of men. Symptoms within 1 month were most frequent in the group residing on an isolated island (74%), followed by the group residing in Kagoshima City (61%), and then the group residing outside of Kagoshima City (55%; P<0.001; Table 1). Ambulance transport was highest for the group residing in Kagoshima City (72.2%) and lowest for the group residing in the isolated islands (52.8%; P<0.001). The use of the doctor helicopter was significantly higher for the group residing on isolated islands (20.0%) than for the group residing outside Kagoshima City (2.8%) or in Kagoshima City (0.4%; P<0.001).

Coronary Risk Factors and Treatment Dyslipidemia was most frequent among patients residing in Kagoshima City (62.3%) and least common among those residing on isolated islands (49.6%; P<0.001), with the use of lipid-lowering drugs highest outside Kagoshima City (79.5%) and lowest on isolated islands (61.3%; P<0.001). There were no significant differences in the prevalence of diabetes according to place of residence (P=0.43), but the use of antidiabetic drugs was lowest on the isolated islands (70%; P=0.008). There were no significant differences in the use of statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and other lipid-lowering drugs among the 3 groups.

Other Complications Acute heart failure differed significantly (P=0.02) according to place of residence and was most frequent in the group residing outside Kagoshima City (13%), followed by Kagoshima City (9.4%) and the isolated islands (12%). Meanwhile, the incidence of cardiac arrest within 24 h was highest among the group residing on isolated islands (5.6%; P=0.03 vs. the other 2 groups).

Lipid Profiles

In the entire study cohort, total cholesterol levels decreased significantly from admission to discharge (from 187.4±48.5 to 140.5±37.9 mg/dL) and remained stable after 3 months (142.5±33.8 mg/dL; Table 2). Similarly, LDL-C levels decreased significantly from admission to discharge (113.3±39.9 and 74.6±28.0 mg/dL, respectively), decreasing further to 69.2±25.9 mg/dL after 3 months (P<0.0001, MANOVA; P_trend<0.0001; Table 2; Figure 3). High-density lipoprotein cholesterol in the entire study cohort initially decreased from 52.5±15.5 mg/dL at admission to 41.9±15.9 mg/dL at discharge, but increased thereafter to 51.2±13.8 mg/dL at 3 months. Triglyceride levels showed a modest decline over time, with median values of 114 mg/dL (IQR 76–175 mg/dL) at admission, 110 mg/dL (IQR 84–145 mg/dL) at discharge, and 106.5 mg/dL (IQR 77–153 mg/dL) at 3 months.

Table 2.

Changes in Lipid Profile and Therapeutics

	At registration	At discharge	At 3 months
Cholesterol levels
Total cholesterol (mg/dL)	187.4±48.5	140.5±37.9	142.5±33.8
LDL-C (mg/dL)	113.3±39.9	74.6±28.0	69.2±25.9
HDL-C (mg/dL)	52.5±15.5	41.9±15.9	51.2±13.8
Triglyceride (mg/dL)	114 [76–175]	110 [84–145]	106.5 [77–153]
Drug-related items
Use of lipid-lowering drugs	460/1,184 (39)	1,039/1,184 (88)	945/1,184 (80)
Statin	417/460 (91)	1,018/1,039 (98)	895/945 (95)
Ezetimibe	111/460 (24)	350/1,039 (31)	385/945 (41)
PCSK9 inhibitor	3/460 (0.7)	3/1,039 (0.3)	11/945 (1.1)
Others	49/460 (11)	23/1,039 (2.0)	34/945 (3.6)
Maximum tolerated doses of high-intensity statin	29/417 (7.0)	45/1,018 (4.4)	83/895 (9.3)

Data are given as the mean±SD, median [interquartile range], or n/N (%). Abbreviations as in Table 1.

Figure 3.

Changes in low-density lipoprotein cholesterol (LDL-C) levels after implementation of the Optimal Therapy for All Kagoshima Acute Coronary Syndrome (OK-ACS) Registry. The boxes show the interquartile range, with the median value indicated by the horizontal line; whiskers show the range. Values below the x-axis are the mean±SD LDL-C level for each time point.

Changes in LDL-C According to Place of Residence

There were no significant differences in LDL-C levels among the 3 places of residence (P=0.14, repeated-measures ANOVA). However, longitudinal reductions in LDL-C were highly significant within each group (P<0.0001, MANOVA; P_trend<0.0001, Bonferroni adjusted; Figure 4).

Figure 4.

Changes in low-density lipoprotein cholesterol (LDL-C) according to place of residence. The boxes show the interquartile range, with the median value indicated by the horizontal line; whiskers show the range. Values below the x-axis are the mean±SD LDL-C level for each time point.

Use of Lipid-Lowering Drugs

In the entire study cohort, the proportion of patients using lipid-lowering drugs increased from 39% at admission to 88% at discharge, then decreased slightly to 80% at 3 months (Table 2). Statin use was consistently high, with 91% of patients using statins at admission, 98% at discharge, and 95% at 3 months (Table 2). Ezetimibe use increased from 24% at admission to 31% at discharge and further to 41% at 3 months (Table 2). The use of PCSK9 inhibitors was minimal, increasing slightly from 0.7% at admission to 1.1% at 3 months (Table 2).

Maximum Tolerated Doses of High-Intensity Statin

The proportion of patients receiving the maximum tolerated dose of high-intensity statin increased over time, from 7.0% at admission to 4.4% at discharge and 9.3% at 3 months (Table 2).

LDL-C Levels <70 mg/dL

The percentage of patients with LDL-C levels <70 mg/dL increased significantly over time. At baseline, only 12% of patients had LDL-C <70 mg/dL; this increase to 47% of patients at discharge and to 59% of patients at 3 months (Figure 5A). These changes were statistically significant (Cochran’s Q test, P<0.0001; P_trend<0.0001), indicating a consistent improvement in LDL-C control over time (Figure 5A).

Figure 5.

Percentage of patients achieving low-density lipoprotein cholesterol (LDL-C) levels (A) <70 mg/dL and (B) <55 mg/dL.

LDL-C Levels <55 mg/dL

The proportion of patients achieving LDL-C levels <55 mg/dL increased significantly over time. At baseline, only 4% of patients had LDL-C levels <55 mg/dL; this increased to 21% of patients at discharge and to 30% of patients at 3 months (Figure 5B). These changes were statistically significant (Cochran’s Q test, P<0.0001; P_trend<0.0001), demonstrating an overall improvement in achieving stricter LDL-C targets over time (Figure 5B).

Clinical Characteristics in Patients With LDL-C Levels <70 and ≥70 mg/dL at 3 Months

Table 3 compares the baseline characteristics of patients with LDL-C levels <70 and ≥70 mg/dL at 3 months. The group with LDL-C levels <70 mg/dL was older and had more myocardial infarctions at presentation, lower baseline LDL-C, and more frequent ezetimibe use. The group with LDL-C levels ≥70 mg/dL had a higher proportion of patients with a poor long-term prognosis. These differences were statistically significant.

Table 3.

Patients Characteristics According to LDL-C Levels <70 and ≥70 mg/dL at 3 Months

	LDL-C <70 mg/dL (n=544)	LDL-C ≥70 mg/dL (n=384)	P value
Age (years)	70±12	68±13	0.03
Male sex	420 (77.2)	297 (77.3)	0.96
Height (cm)	161.9±9.7	162.2±9.5	0.58
Weight (kg)	64.2±13.3	64.8±13.7	0.51
BMI (kg/m²)	24.3±3.9	24.4±3.7	0.64
Pulse rate (beats/min)	80.6±21.4	78.2±19.5	0.08
Systolic blood pressure (mmHg)	139.6±27.9	140.9±30.8	0.52
Diastolic blood pressure (mmHg)	83.4±17.6	84.6±20.1	0.35
Emergency revascularization	523 (96.1)	345 (89.8)	<0.001
Cardiopulmonary arrest within 24 h	20 (3.7)	7 (1.8)	0.09
Cardiogenic shock within 24 h	44 (8.1)	28 (7.3)	0.45
Acute heart failure within 24 h	50 (9.2)	46 (12)	0.14
Symptoms within 1 month	345 (63)	228 (59)	0.45
Walk-in visit	127 (23.3)	117 (30.5)	0.02
Ambulance transport	387 (71.1)	254 (66.2)	0.11
Doctor helicopter use	29 (5.3)	10 (2.6)	0.04
Doctor helicopter flight time (h)	9.5 [7.75–30.5]	23.5 [5.5–29]	0.63
After-hours service	285 (52.4)	188 (49.0)	0.34
Referrals from other hospitals	284 (52.2)	170 (44.3)	0.02
Diagnosis
Acute myocardial infarction	476 (87.5)	307 (80.0)	0.008
ST-elevation type	371 (77.9)	235 (76.6)
Non-ST-elevation type	105 (22)	72 (23)
Unstable angina pectoris	66 (12.1)	75 (19.5)
Other	2 (0.4)	2 (0.5)
Cardiopulmonary arrest	0 (0)	0 (0)
Drinking alcohol	202 (37.1)	140 (36.5)	0.29
Smoker	274 (50.4)	218 (56.8)	0.05
Hypertension	395 (72.6)	258 (67.2)	0.2
Use of antihypertensive drugs	344/395 (87.1)	221/258 (85.7)	0.18
Diabetes	216 (39.7)	132 (34.4)	0.22
Use of antidiabetic drugs	171/216 (79.2)	103/132 (78.0)	0.25
Dyslipidemia	294 (54.0)	229 (59.6)	0.09
Familial hyperlipidemia	0 (0)	0 (0)	–
Use of lipid-lowering drugs	210 (38.6)	164 (42.7)	0.24
Statin	193 (91.9)	143 (87.2)	0.13
Ezetimibe	65 (31.0)	30 (18.3)	0.005
PCSK9 inhibitor	2 (1.0)	0 (0)	0.21
Others	20 (9.5)	16 (9.8)	0.94
Maximum tolerated dose of high-intensity statin	18/193 (9.3)	6/143 (4.1)	0.07
COVID-19 test at visit	366 (67.3)	294 (76.6)	0.008
COVID-19 test result (positive)	8 (2.3)	7 (2.4)	0.87
LVEF^A (%)	52.6±12.5	53.4±12.3	0.38
Previous history
History of bleeding	12 (2.2)	7 (1.8)	0.44
History of atrial fibrillation	31 (5.7)	24 (6.2)	0.64
Type of atrial fibrillation
Paroxysmal atrial fibrillation	18 (3.3)	16 (4.2)	0.7
Persistent atrial fibrillation	4 (0.7)	1 (0.3)
Chronic atrial fibrillation	9 (1.7)	7 (1.8)
History of myocardial infarction	71 (13.1)	40 (10.4)	0.34
History of heart failure	39 (7.2)	20 (5.2)	0.48
History of stroke	51 (9.4)	38 (9.9)	0.17
History of malignancy	44 (8.1)	33 (8.6)	0.64
History of active malignancy	11 (2.0)	7 (1.8)	0.13
History of poor long-term prognosis	9 (1.7)	20 (5.2)	0.01
History of PCI	95 (17.5)	63 (16.4)	0.74
POBA only	3 (3.2)	3 (4.8)	0.56
Stenting	90 (94.7)	57 (90.5)
Details unknown	2 (2.1)	3 (4.8)
History of CABG	14 (2.6)	8 (2.1)	0.85
Complications of PAD	20 (3.7)	9 (2.3)	0.36
Complications of aortic aneurysm/dissection	20 (3.7)	9 (2.3)	0.36
Complications of chronic liver disease	10 (1.8)	5 (1.3)	0.78
Maintenance dialysis	24 (4.4)	6 (1.6)	0.02
Complications of COPD	8 (1.5)	9 (2.3)	0.53
Laboratory data at registration
White blood cell count (μL)	8,915 [6,608–11,600]	8,750 [6,545–11,300]	0.63
Hemoglobin (g/dL)	13.7±2.0	13.9±2.3	0.11
Platelet (μL)	22.1 [17.2–26.8]	21.5 [18.1–25.2]	0.55
Creatinine (mg/dL)	0.92 [0.76–1.18]	0.87 [0.71–1.09]	0.04
eGFR (mL/min/1.73 m²)	59.5±23.7	63.8±24.6	0.007
HbA1c (NGSP) (%)	6.1 [5.7–6.8]	6.0 [5.6–6.5]	0.01
Glycoalbumin (%)	17.1±7.0	–	–
Total cholesterol (mg/dL)	181.7±48.4	199.6±50.7	<0.001
HDL-C (mg/dL)	52.6±15.9	52.2±14.3	0.71
Triglyceride (mg/dL)	114 [78–166]	127 [75–197]	0.16
LDL-C (mg/dL)	106.2±38.7	124.9±41.0	<0.001
CRP (mg/dL)	0.17 [0.07–0.60]	0.17 [0.06–0.54]	0.18
BNP (pg/mL)	77.8 [22.9–248]	64.9 [21.8–212.7]	0.18
NT-proBNP (pg/mL)	408 [107–1,720]	433.5 [85.5–1,133]	0.53
Albumin (g/dL)	3.9±0.6	4.1±2.2	0.24

Unless indicated otherwise, data are presented as n (%) for categorical variables and as the median [interquartile range] or mean±SD for continuous variables. Two-tailed P<0.05 was considered significant. ^ALVEF was evaluated by cardiac echocardiography. BNP, B-type natriuretic peptide; COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; NT-proBNP, N-terminal pro B-type natriuretic peptide; POBA, plain old balloon angioplasty. Other abbreviations as in Table 1.

Discussion

In this study, we found that: (1) there were clear differences in background, treatment/management, and access to medical care among ACS patients according to their place of residence in Kagoshima Prefecture; and (2) LDL-C levels were significantly reduced at the time of discharge and 3 months after discharge, and that implementing the Kagoshima Style pathway resulted in increased achievement of LDL-C targets.

Place of Residence in Kagoshima Prefecture

Geographic Disparities in Presentation and Access to Care There are challenges to the treatment of myocardial infarction in remote islands, such as a lack of specialized medical facilities, long-distance patient transport, and organization of an emergency medical system. These challenges are barriers to providing rapid reperfusion therapy in the treatment of myocardial infarction.¹⁵^,¹⁶ The results of the present study highlight significant geographic disparities in the presentation and management of patients with ACS across Kagoshima Prefecture. Patients from isolated islands had the highest prevalence of symptoms within 1 month (74%) and were more likely to require helicopter transport (20%). The study findings underscore the challenges faced by residents of remote areas in accessing timely healthcare. In contrast, patients from Kagoshima City had the highest ambulance transport rate (72.2%), reflecting better access to emergency medical services in urban settings. In addition, a significantly higher proportion of patients experienced symptoms within 1 month on isolated islands (74%) than in Kagoshima City (61%), suggesting that patients on isolated islands may be tolerating their symptoms due to problems with access to medical care. These findings emphasize the need to strengthen healthcare infrastructure and emergency response systems in remote regions. Furthermore, cardiopulmonary arrest within 24 h occurred more frequently on remote islands, indicating a higher severity of ACS in these areas. Differences in prognosis and treatment outcomes for ACS patients have been reported between rural and urban areas, as well as between high-volume PCI centers and regional hospitals.¹⁷^,¹⁸ Cases of severe ACS requiring advanced mechanical circulatory support remain challenging, particularly in remote areas with limited access.¹⁹ In addition, the presence or absence of clinical symptoms in ACS patients influences prognosis.²⁰ Further investigations are needed to validate these findings.

Cardiovascular Risk Factors and Treatment Patterns The prevalence of hypertension and diabetes was high across all regions, but the use of antidiabetic drugs was significantly lower in the isolated island group (70%) compared with the other 2 groups (P=0.008). Similarly, dyslipidemia was the least common in the isolated island group (49.6%) and most prevalent in the Kagoshima City group (62.3%; P<0.001). However, the use of lipid-lowering drugs, including statins, was lowest in the isolated island group (61.3%), suggesting regional variations in treatment practices or clinical inertia.²¹^,²² These findings suggest that healthcare access, resource availability, and adherence to treatment guidelines may vary by region.

Lipid Management

Intensive lipid-lowering therapy targeting LDL-C significantly reduces the risk of CAD and induces plaque regression.⁴^,⁵^,²³^–²⁵ Statins decrease the risk of major cardiovascular events by 21% and CAD-related mortality by 19%.⁵^,²⁶^,²⁷ Combining statins with ezetimibe or PCSK9 inhibitors further reduces cardiovascular events.²⁸^–³² In ACS patients, recurrent cardiovascular events often arise from untreated lesions, making aggressive lipid-lowering therapy crucial for secondary prevention.³³ Current Japanese guidelines recommend targeting LDL-C <70 mg/dL and using high-intensity statins from the acute phase.¹⁰^,¹¹ However, adherence to these guidelines in clinical practice remains suboptimal, with only 50% of patients achieving LDL-C levels <70 mg/dL despite guideline-directed therapy.¹³^,¹⁴

In this study, we introduced the Kagoshima Style regional lipid management pathway to all PCI facilities in Kagoshima Prefecture. Our findings showed that implementing this pathway led to significant reductions in LDL-C levels at discharge and 3 months after discharge, improving the achievement rate of LDL-C target levels. This trend remained consistent even when assuming the European guideline target of LDL-C <55 mg/dL.³⁴^,³⁵ Conversely, a study of Korean patients with ACS reported no additional benefit in setting the LDL-C target to <55 vs. <70 mg/dL.³⁶ In the future, we plan to evaluate lipid management and its impact on prognosis by using data from the OK-ACS Registry.

In Europe, it has been suggested that by ensuring optimal treatment during hospitalization for ACS and implementing dedicated follow-up protocols, lipid levels may be significantly improved, potentially reducing the risk of future recurrence.³⁷^,³⁸ In Japan, it has been reported that implementing lipid management protocols and sharing clinical pathways across facilities improves LDL-C <70 mg/dL achievement, particularly in patients with ACS receiving intensive statin therapy at discharge.³⁹^,⁴⁰ However, maintaining intensive lipid-lowering therapy after the acute phase remains challenging.⁴¹ A European survey highlighted areas for improvement in LDL-C follow-up, including insufficient prescriptions at discharge, lack of patient education, and limited communication with family physicians about guidelines.⁴² Conversely, it was shown that regularly checking guideline recommendations during follow-up can help achieve target LDL-C levels.⁴³ The Kagoshima Style facilitated collaboration between PCI facilities and local primary care physicians, reducing variability of treatment among physician. By promoting shared follow-up and providing clear medication guidance, our structured approach contributed to better outcomes. However, only 4.4% of patients were discharged on the guideline-recommended maximum tolerated doses of high-intensity statin, which is insufficient. These findings highlight the challenges in achieving and maintaining an LDL-C target of <70 mg/dL with a high success rate.

Further Improvements in Lipid Management

Although 59% of patients achieved the treatment goal at 3 months, an improvement over previous studies, this remains below the guideline target. Further improvements are required. Although the Kagoshima Style pathway has been successfully implemented as a regional pathway, it is not included in the official clinical guidelines. Moving forward, institutional and regional commitment to lipid management goals should be strengthened through collaboration between cardiologists and general practitioners. A comprehensive approach, including early initiation of ezetimibe and PCSK9 inhibitors alongside statins, a “strike early, strike strong” strategy, may improve the achievement of LDL-C goals.⁴⁴ However, cost-effectiveness remains a barrier, and thoughtful strategies to overcome these financial limitations will be necessary to align with European and US guidelines. At the time when the OK-ACS Registry was started, awareness regarding the use of PCSK9 inhibitors was still limited in Kagoshima Prefecture. There was significant resistance to their early use in patients with ACS. In addition, financial concerns regarding the high cost of PCSK9 inhibitors were a major barrier, particularly for patients from rural areas and remote islands, where the resistance to high medical expenses remains strong. These factors likely contributed to the low usage rate of PCSK9 inhibitors in our study.⁴⁵ Conversely, real-time LDL-C monitoring through electronic medical records or cloud-based systems, along with patient education materials such as brochures and videos, may improve adherence and optimize lipid management. We analyzed the baseline characteristics of patients stratified by LDL-C levels at 3 months to better understand factors associated with lipid-lowering therapy outcomes (Table 3). Our findings suggest that more intensive lipid-lowering strategies may have been used for older patients and those with myocardial infarction at presentation. Conversely, the higher proportion of patients with poor long-term prognosis in the LDL-C ≥70 mg/dL group may indicate a more conservative approach to lipid management. These associations warrant further investigation to better understand their clinical implications and inform future treatment strategies.

Our findings emphasize the importance of structured lipid management pathways, such as the Kagoshima Style, in ensuring consistent care for patients with ACS. In isolated islands, limited numbers of PCI facilities and primary care cardiologists pose a challenge to optimal lipid management. The Kagoshima Style pathway improved coordination between PCI facilities and primary care physicians, enhancing lipid management even in remote areas. A recent survey found that regional collaborative pathways for patients with ACS were established in only approximately one-third of Japan’s prefectures.¹² Expanding and refining such pathways at the national level may improve guideline adherence and improve long-term outcomes. Future research should explore the adaptability of this approach in diverse healthcare settings.

Public Health and Clinical Implications

The findings of this study have important implications for public health and clinical practice. Addressing geographic disparities in access to care is critical, particularly in isolated areas where healthcare delivery may be delayed. Enhancing adherence to evidence-based therapies, including lipid-lowering and antidiabetic medications, is essential to improving outcomes in underserved populations. Furthermore, the success in achieving lipid control underscores the importance of aggressive risk factor management in patients with acute cardiovascular conditions.

Study Limitations

This study has several limitations. The observational design of the study limits causal inferences, and the analyses do not account for all potential confounders. Furthermore, this study is an interim analysis of a long-term observational study and lacks long-term follow-up data beyond 3 months, which may underestimate the impact of the intervention. In addition, 652 patients were excluded due to incomplete data, which may have introduced sampling bias. Finally, because this study is based on data from Kagoshima Prefecture, its applicability to other regions or countries is unknown.

Conclusions

The regional medical care gap and lipid management in patients with ACS in Kagoshima Prefecture remain insufficient. Education of local medical institutions is crucial to achieving early and sustained reductions in LDL-C levels. Based on the results of our study, actively promoting the implementation of clinical pathways, which foster a shared understanding among multiple physicians and ensure consistent patient management, is particularly important. Furthermore, additional research and analyses are planned of the OK-ACS Registry to investigate risk stratification within patient populations and to assess the effect on prognosis.

Kagoshima Prefecture consists of 2 peninsulas and numerous remote islands that are inhabited, highlighting the complexity of medical systems and patient transportation across different regions in addressing ACS. Further detailed investigations will be conducted to explore these challenges.

Acknowledgments

The authors thank all the participating hospitals and members of the OK-ACS Registry group in Kagoshima for their efforts, as well as the staff of the Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, for their assistance.

Sources of Funding

This study was funded by Amgen K.K. and Astellas Pharma Inc. These funders did not have access to the original data.

Disclosures

M.O. is a member of Circulation Journal’s Editorial Team. All other authors declare that they have no conflicts of interests.

IRB Information

This study was approved by the Kagoshima University Hospital Ethics Committee (Approval no. 210251).

Data Availability

The deidentified participant data will not be shared.

Supplementary Files

Please find supplementary file(s);

https://doi.org/10.1253/circj.CJ-25-0083

References

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